Event Details

Structure, dynamics and function of intrinsically disordered proteins from experiment and molecular simulation

Description:

Intrinsically disordered proteins are recognized to play key biological roles, however current structural biology and simulation techniques are often poorly suited to characterizing them. Experimental methods such as Förster resonance energy transfer (FRET), nuclear magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering (SAXS) can all yield useful information, but are averaged over a very heterogeneous structural ensemble, making interpretation difficult. Here, I illustrate how molecular simulation can be used as an aid in determining a molecular model reflecting the structural and dynamic properties observed in experiment. In particular, I will focus on the recently discovered example of two intrinsically disordered proteins which bind with 1:1 stoichiometry to form a complex with nanomolar affinity mediated by the opposing charges of the molecules. Coarse-grained molecular simulations with a simple empirical potential are able to explain a range of FRET and NMR data for the complex. Remarkably, they reveal that both proteins remain essentially completely disordered when bound -- results which are backed up by independent all-atom simulations of the same complex. This raises the question of how frequent such fully disordered complexes may be in biology.